Influence of the magnesium aspartate hydrochloride administration to the maternal circuit on the aspartate concentration of the fetal circuit under in vitro perfusion of human placenta.
OBJECTIVE
Magnesium aspartate hydrochloride (Magnesiocard, Mg-Asp-HCl) is proposed as a substitute of magnesium sulfate for the treatment of preeclampsia and premature labor. After an i.v. administration of a dose equivalent to that used in the treatment of preeclampsia to nonpregnant volunteers, a 10-fold increase of aspartic acid (Asp) over the physiological level was observed. Animal experiments have demonstrated that highly increased fetal levels of acidic amino acids such as Asp could be associated with neurotoxic damage in the fetal brain. The influence of such an elevation of Asp concentration in the maternal circuit on the fetal level, using the in vitro perfusion model of human placenta, was investigated.


METHODS
After a control phase (2h), a therapeutic dose of Mg combined with Asp (Magnesiocard, Mg-Asp-HCl) was applied to the maternal circuit approaching 10 times the physiological level of Asp. The administration was performed in two different phases simulating either a peak of maximum concentration (bolus application, 2h) or a steady state level (initially added, 4h).


RESULTS
In four experiments, during experimental phases (6h) a slow increase in concentration in the fetal circuit was seen for Mg, AIB (alpha-aminoisobutyric acid, artificial amino acid) and creatinine confirming previous observations. In contrast, no net transfer of Asp across the placenta was seen. A continuous decrease in the concentration of Asp on both maternal and fetal side suggests active uptake and metabolization by the placenta. Viability control parameters remained stable indicating the absence of an effect on placental metabolism, permeability and morphology.


CONCLUSIONS
Elevation of Asp concentration up to 10 times the physiological level by the administration of Mg-Asp-HCl to the maternal circuit under in vitro perfusion conditions of human placenta has no influence on the fetal level of Asp suggesting no transfer of Asp from the maternal to fetal compartment. Therefore, the administration of Mg-Asp-HCl to preeclamptic patients would be beneficial for the patients without any impact on placental or fetal physiology.
Malek
A
A
Department of Obstetrics and Gynecology, University of Berne, Inselspital, Switzerland. Antoine.malek1@gmail.com
Leiser
R
R
D000621:Aminoisobutyric Acids / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism* / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000188:drug therapy; D011247:Pregnancy
D000621:Aminoisobutyric Acids; C100049:2-aminoisobutyric acid; D001224:Aspartic Acid